A variety of projects are underway to develop a greater understanding of the mechanisms of various antitumor agents to improve upon the efficacy of clinical chemotherapeutic trials with these agents. Ongoing work with the antifolate compounds, nitrosoureas, vinca alkaloids, 5-FU, and the platinum coordination compounds has been carried out the past year and will continue. In vitro studies are being conducted to elucidate the possible role of drugs which expedite methotrexate transport, specifically the vinca alkaloids. The biological properties of nitrosourea derivative are under study, and a new non-myelosupressive analogue, chlorozotocin, has entered clinical trials during the past year. Pharmacokinetic evaluation of this agent has been begun. Methods are being developed to assay the various metabolites of 5-fluorouracil, as well as the metabolites of the normal pyrimidine precursors of nucleic acids. The platinum coordination compounds are being investigated to determine the mechanisms of binding to nucleic acids and/or nuclear histone proteins. The nitrosoureas are being evaluated in terms of immunosuppressive characteristics. The work will be carried out in terms of transport of nitrosoureas into the central nervous system and other tissues.